The antifungal activity of oleylphosphocholine (OlPC) on in vitro and in vivo Candida albicans biofilms [PublishAheadOfPrint]

In this study, we investigated the potential antifungal activity of the alkylphospholipid - oleylphosphocholine (OlPC), a structural analogue of miltefosine, on in vitro and in vivo Candida albicans biofilm formation. The effect of OlPC on in vitro and in vivo C. albicans biofilms was studied inside triple-lumen polyurethane catheters. In vivo biofilms were developed subcutaneously after catheter implant on the lower back of Sprague Dawley rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7 days. The effect of OlPC on biofilms developed on mucosal surface was studied in an ex vivo model of oral candidiasis. The role of OlPC on C. albicans morphogenesis was investigated in hyphae-inducing media namely, Lee, Spider and RPMI 1640. OlPC displayed activity against both planktonic cells and in vitro C. albicans biofilms. To completely abolish preformed, 24 h old biofilms, higher concentrations (8, 10 and 13 mg/L) were needed. Moreover, OlPC was able to reduce C. albicans biofilms formed by caspofungin-resistant clinical isolates and acted synergistically when combined with caspofungin. Daily administration of OlPC orally, significantly reduced in vivo C. albicans biofilms developed subcutaneously. In addition, OlPC decreased biofilm formation on mucosal surfaces. Interestingly, application of sub-inhibitory concentrations of OlPC already inhibited the yeast-to-hyphae transition, a crucial virulence factor of C. albicans. We document, for the first time, the effects of OlPC on C. albicans cells and suggest the potential use of OlPC in the treatment of C. albicans biofilm-associated infections.

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